MSH6 (MutS homolog 6)

P2, N=2, Active, not recruiting, National Cancer Institute (NCI) | N=240 --> 2 | Trial completion date: Oct 2027 --> Jun 2027 | Trial primary completion date: Oct 2027 --> Jan 2026

The findings favored metastatic colorectal carcinoma involving the pancreas in the setting of clinically suspected Lynch syndrome. This case emphasizes the importance of clinicopathologic correlation, cautious interpretation of MMR deficiency, and long-term multidisciplinary surveillance.

In this retrospective cross-sectional study, cascade testing was underused, especially among specific demographic groups, with clinical and cultural factors appearing to play a larger role than financial barriers. These findings may guide efforts to address barriers preventing wider uptake of cascade testing and improve cancer prevention efforts, particularly among racial and ethnic minority groups.

Understanding its histological features and immunohistochemical profile facilitates its diagnosis and differential diagnosis, including CK20 positivity and Ki-67 negativity in the superficial layer, and high Ki-67 expression with negative CK20 staining in the deep layer. KRAS gene mutation is also an important diagnostic feature.

These findings support the value of routine IHC-based MMR testing in CRC patients. However, confirmatory molecular testing (e.g., MSI analysis, BRAF V600E mutation, MLH1 promoter methylation, or germline sequencing) is necessary to differentiate sporadic from Lynch syndrome-associated dMMR cases and to fully guide Lynch syndrome screening and immunotherapy decisions.

This enabled the decision to treat with immunotherapy for recurrence and also conduct family screening. In spite of the absence of colonic tumours, Lynch syndrome should be suspected in young patients with multiple tumours, particularly when supported by a relevant family history.

P2, N=76, Recruiting, Dechang Diao

Additional variants in MSH6 and CTU2 were also identified and may act as potential modifiers of disease susceptibility, consistent with a multigenic contribution to TGCT risk. These findings support a contributory role for the PDE11A locus in TGCT predisposition and underscore the biological relevance of overlapping sense-antisense genomic regions in hereditary cancer studies.

The worse outcomes of rectal MAC appear to be driven largely by late-stage presentation, possibly owing to later diagnosis. MAC nonetheless carries a distinct immune phenotype, detectable even in histologically normal surrounding mucosa, that likely contributes to its treatment resistance. These observations provide a basis for developing histotype-specific approaches to both early detection and treatment in this uncommon but clinically challenging tumour subtype.

The findings underscore the limitations of tumor-only sequencing and current variant interpretation frameworks in admixed populations. Larger studies integrating matched normal DNA, ancestry-informed analyses, functional validation, and broader sequencing strategies could help improve variant interpretation in Latin American populations.

Here, we report a patient with locally advanced Gleason 5 + 5 = 10 prostatic adenocarcinoma harboring MSH2 and MSH6 genomic deletions with ultrahigh TMB (>250 mutations/megabase) in whom pembrolizumab resulted in a striking complete radiographic, pathologic, and molecular response...Similar T cells are also present in diverse cancers and expand exclusively in ICI-responsive patients. These findings inform on the cellular mechanisms by which immunotherapies may mediate profound responses in patients with dMMR solid tumors.